Hello everyone,
I´m trying to orientate in the problematics of cholesterol metabolism. I´ve heard there are crucial differences between cholesterol metabolism in mouse and human, but I can´t find any paper, which would compare this issues clearly and simply. Could you please post here link to paper which could help, or any general ideas in which particular enzymes, pathways, molecules... does the cholesterol metabolism between mouse and human differ? I hope this could help a lot of people as well as me ;) Thank you very much!
To be honest this is not a very clever question. Mice do not have CETP. As a consequence they have HDL as major cholesterol carrying lipoproteins. This is completely different from lipoprotein metabolism in humans. Moreover environmental differences and genetic makeup will influence lipoprotein metabolism. If you want to read papers you have to go back to literature published in the sixties and seventies.
I agree with Geesja Dallinga-Thie - although there are several studies performed in transgenic mice to better mimic the human situation. For example LDLR knockout mice and apoE ko mice (often double ko are used) which develop atherosclerosis. There is a huge amount of literature available on this topic if you search in NCBI, not going back that early as the 60ies and 70ies....;-)
It is better to find out the similarities of cholesterol metabolism between mice and human, which I believe is more significant than to seek the differences in terms of basic scientific research. Of course, the human specific cholesterol metabolism does provide some valuable information for therapeutical aspect, which could not be projected properly by mouse disease models, and therefore, primate model for cholesterol metabolism disorders may be better option in this case.
Let him search for more information in Pubmed articles as suggested earlier
Well, "search on pubmed" is not realy helpful advice, as of course, if one wants to find some answers, the first thing one usually does is "searching on pubmed", so not that I haven´t tried yet :) But imagine you work with something completly different and you want to discover the area, which is entirely new to you. You don´t know where to start and pubmed just gets you confused by huge amount of details.
What I´m asking - and maybe it is not clever question, but I can´t tell - is this: If I read some review of cholesterol metabolism which includes cholesterol absorption, synthesis, traficking in blood and excretion.. can I apply this general information on mouse model, or is it so different from human cholesterol metabolism, that this patways I´m reading about probably don´t appear in mice?
Like "mouse don´t have CETP, while human have" seems a good information for me.
Liver X receptors (LXRs) are key regulators of expression of the genes. In rodents but not in humans, LXR activation enhances hepatic cholesterol catabolism partly through increased expression of cytochrome P450 7A1, the rate-limiting enzyme in the classic conversion of cholesterol to bile acids. Apolipoprotein B (APOB or ApoB) is the primary apolipoprotein of low-density lipoproteins. Mice overexpressing mApoB have increased levels of LDL "bad cholesterol" and decreased levels of HDL "good cholesterol". Homozygous male and female mice lacking LDL receptors. >90% of human HDL-C quantitative trait locus have homologous quantitative trait locus in mice. The cholesterol ester transfer protein (CETP) facilitates the transfer of HDL cholesterol esters from plasma to the liver. Transgenic mice expressing human CETP, controlled by its natural flanking region, increase expression of this gene in response to hypercholesterolemia. CETP is synthesized in liver and small intestine as well as a number of peripheral tissues. Mice do not have plasma CETP activity.
Hi Jana R.
You think ''"search on pubmed" is not realy helpful advice''?
The topic is just far too complex! To provide answers here we would have to spend a lot of time writing - which none of us has :-)
Start with the reviews, there is plenty around! And read, read, read!
Good luck,
Ute
Though it resembles closely with human system it might me different slightly. i feel
It may be relevant to consider that mice are herbivores, unlike humans and rats, and therefore probably encounter little or no dietary cholesterol in the wild. As such, regulation might be biased toward the anabolic pathways with relatively less control over catabolism. Note also that the lack of a gall bladder in rats may have been an evolutionary driver for the complexity of the promoter for the ileal sodium/bile acid transporter gene (Slc10a2 or ASBT). Dave
Old question, but for anyone who comes looking for help here is a relevant publication with rats http://onlinelibrary.wiley.com/doi/10.1002/ejlt.200700280/abstract
wow, amazing how annoyed scientists can get when their whole field gets boiled down to just one question. I suggest you answer the researcher instead of attacking her. Or be quiet.
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